Methyl iodide → 1-Boc-3-(MethoxyMethyl)piperazine

HRID 1772832Notes

Reaction equation

HRID 1772832 reaction equation
[H-].[Na+].[OH:3][CH2:4][CH:5]1[NH:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1.[CH3:18]I>C1COCC1>[CH3:18][O:3][CH2:4][CH:5]1[NH:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 223865084-N-Boc-2-hydroxymethylpiperazine

Product 1

HCID 578869141-Boc-3-(MethoxyMethyl)piperazine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of sodium hydride (0.10 g, 2.6 mmol, 60% in mineral oil) in THF (6.0 mL) at 0° C., was treated with a solution of tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (0.56 g, 2.6 mmol, racemic, AstaTech) in THF (6.0 mL). After 15 min, methyl iodide (0.16 mL, 2.6 mmol) was added. The mixture was allowed to warm to RT and stir for 1.5 h. The reaction was then quenched with water, and extracted with four portions of DCM. The combined extracts were dried over sodium sulfate, decanted and concentrated. Flash chromatography using a 40 g silica gel cartridge, eluting with a gradient from 0-15% MeOH in DCM afforded the purified desired product, as the second product to elute (60 mg, 10%). 1H NMR (500 MHz, CDCl3): δ 3.90 (br s, 2H), 3.37 (dd, 1H), 3.34 (s, 3H), 3.25 (dd, 1H), 2.99-2.92 (m, 1H), 2.90-2.79 (m, 2H), 2.72 (td, 1H), 2.57 (br s, 1H), 2.15 (br s, 1H), 1.45 (s, 9H); LCMS (M+H)+: 231.2.

Workup

  1. customThe reaction was then quenched with water
  2. extractionextracted with four portions of DCM
  3. dry with materialThe combined extracts were dried over sodium sulfate
  4. customdecanted
  5. concentrationconcentrated
  6. washeluting with a gradient from 0-15% MeOH in DCM
  7. customafforded the
  8. custompurified desired product
  9. washas the second product to elute (60 mg, 10%)

Sources & evidence

ORD record
ord-236dedf913a04f908b060c6f3b012a7b
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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